Prediction of key amino acids of Salmonella phage endolysin LysST-3 and detection of its mutants' activity.

Salmonella Typhimurium, a zoonotic pathogen, causes systemic and localized infection. The emergence of drug-resistant S. Typhimurium has increased; treating bacterial infections remains challenging. Phage endolysins derived from phages have a broader spectrum of bacteriolysis and better bacteriolytic activity than phages, and are less likely to induce drug resistance than antibiotics. LysST-3, the endolysin of Salmonella phage ST-3, was chosen in our study for its high lytic activity, broad cleavage spectrum, excellent bioactivity, and moderate safety profile. LysST-3 is a promising antimicrobial agent for inhibiting the development of drug resistance in Salmonella. The aim of this study is to investigate the molecular characteristics of LysST-3 through the prediction of key amino acid sites of LysST-3 and detection of its mutants' activity. We investigated its lytic effect on Salmonella and identified its key amino acid sites of interaction with substrate. LysST-3 may be a Ca2+, Mg2+ - dependent metalloenzyme. Its concave structure of the bottom "gripper" was found to be an important part of its amino acid active site. We identified its key sites (29P, 30T, 86D, 88 L, and 89 V) for substrate binding and activity using amino acid-targeted mutagenesis. Alterations in these sites did not affect protein secondary structure, but led to a significant reduction in the cleavage activity of the mutant proteins. Our study provides a basis for phage endolysin modification to target drug-resistant bacteria. Identifying the key amino acid site of the endolysin LysST-3 provides theoretical support for the functional modification of the endolysin and the development of subsequent effective therapeutic solutions.

Two novel bacteriophages isolated from the environment that can help control activated sludge foaming.

Nocardia spp., which belongs to one of the Nocardio-form filamentous bacteria, is usually surface hydrophobic and when overproduced attaches to the surface of bubbles under the action of surfactants, allowing the stable presence of foam on the surface of aeration tanks, leading to the occurrence of sludge-foaming events. Two novel phages, P69 and KYD2, were isolated from the environment, and their hosts were Nocardia transvalensis and Nocardia carnea, respectively. These two phages are Siphophages-like with long tails. An aeration tank pilot plant was constructed in the laboratory to simulate sludge foaming, and these two strains of phage were applied. Compared with the reactor not dosed with phage, the application of phage could reduce the host level in the reactor, resulting in the highest decrease in turbidity by more than 68% and sludge volume index by more than 25%. The time for surface foam disappearance was 9 h earlier than that of the control group (the group with the same concentration of Nocardia carnea but no bacteriophage applied), significantly improving water quality. The phage can effectively inhibit the propagation of Nocardia in the actual sludge-foaming event, control the sludge foaming, and improve the effluent quality. It provides a novel and relatively economical solution for controlling sludge foaming in sewage treatment plants in the future, shows that the phages have potential application value in the prevention and control of Nocardia, and provides another way to control the sludge-foaming event caused by the excessive reproduction of Nocardia in the future.

Effectiveness of CT radiomic features combined with clinical factors in predicting prognosis in patients with limited-stage small cell lung cancer.

BACKGROUND: The prognosis of SCLC is poor and difficult to predict. The aim of this study was to explore whether a model based on radiomics and clinical features could predict the prognosis of patients with limited-stage small cell lung cancer (LS-SCLC). METHODS: Simulated positioning CT images and clinical features were retrospectively collected from 200 patients with histological diagnosis of LS-SCLC admitted between 2013 and 2021, which were randomly divided into the training (n = 140) and testing (n = 60) groups. Radiomics features were extracted from simulated positioning CT images, and the t-test and the least absolute shrinkage and selection operator (LASSO) were used to screen radiomics features. We then constructed radiomic score (RadScore) based on the filtered radiomics features. Clinical factors were analyzed using the Kaplan-Meier method. The Cox proportional hazards model was used for further analyses of possible prognostic features and clinical factors to build three models including a radiomic model, a clinical model, and a combined model including clinical factors and RadScore. When a model has prognostic predictive value (AUC > 0.7) in both train and test groups, a nomogram will be created. The performance of three models was evaluated using area under the receiver operating characteristic curve (AUC) and Kaplan-Meier analysis. RESULTS: A total of 1037 features were extracted from simulated positioning CT images which were contrast enhanced CT of the chest. The combined model showed the best prediction, with very poor AUC for the radiomic model and the clinical model. The combined model of OS included 4 clinical features and RadScore, with AUCs of 0.71 and 0.70 in the training and test groups. The combined model of PFS included 4 clinical features and RadScore, with AUCs of 0.72 and 0.71 in the training and test groups. T stages, ProGRP and smoke status were the independent variables for OS in the combined model, whereas T stages, ProGRP and prophylactic cranial irradiation (PCI) were the independent factors for PFS. There was a statistically significant difference between the low- and high-risk groups in the combined model of OS (training group, p < 0.0001; testing group, p = 0.0269) and PFS (training group, p < 0.0001; testing group, p < 0.0001). CONCLUSION: Combined models involved RadScore and clinical factors can predict prognosis in LS-SCLC and show better performance than individual radiomics and clinical models.

Metagenome sequencing reveals shifts in phage-associated antibiotic resistance genes from influent to effluent in wastewater treatment plants.

Antibiotic resistance poses a significant threat to global health, and the microbe-rich activated sludge environment may contribute to the dissemination of antibiotic resistance genes (ARGs). ARGs spread across various bacterial populations via multiple dissemination routes, including horizontal gene transfer mediated by bacteriophages (phages). However, the potential role of phages in spreading ARGs in wastewater treatment systems remains unclear. This study characterized the core resistome, mobile genetic elements (MGEs), and virus-associated ARGs (vir_ARGs) in influents (Inf) and effluents (Eff) samples from nine WWTPs in eastern China. The abundance of ARGs in the Inf samples was higher than that in the Eff samples. A total of 21 core ARGs were identified, accounting for 38.70 %-83.70 % of the different samples. There was an increase in MGEs associated with phage-related processes from influents to effluents (from 12.68 % to 21.10 %). These MGEs showed strong correlations in relative abundance and composition with the core ARGs in the Eff samples. Across the Inf and Eff samples, 58 unique vir_ARGs were detected, with the Eff samples exhibiting higher diversity of vir_ARGs than the Inf samples. Statistical analyses indicated a robust relationship between core ARG profile, MGEs associated with phage-related processes, and vir_ARG composition in the Eff samples. Additionally, the co-occurrence of MGEs and ARGs in viral genomes was observed, ranging from 22.73 % to 68.75 %. This co-occurrence may exacerbate the persistence and spread of ARGs within WWTPs. The findings present new information on the changes in core ARGs, MGEs, and phage-associated ARGs from influents to effluents in WWTPs and provide new insights into the role of phage-associated ARGs in these systems.

Prediction of transition metal carbonitride monolayers MN4C6 (M = Cr, Mn, Fe, and Co) made up of a benzene ring and a planar MN4 moiety.

Based on first-principles calculations, we predict a class of graphene-like magnetic materials, transition metal carbonitrides MN4C6 (M = Cr, Mn, Fe, and Co), which are made up of a benzene ring and an MN4 moiety, two common planar units in the compounds. The structural stability is demonstrated by the phonon and molecular dynamics calculations, and the formation mechanism of the planar geometry of MN4C6 is ascribed to the synergistic effect of sp2 hybridization, M-N coordination bond, and π-d conjugation. The MN4C6 materials consist of only one layer of atoms and the transition metal atom is located in the planar crystal field, which is markedly different from most two-dimensional materials. The calculations indicate that MnN4C6, FeN4C6, and CoN4C6 are ferromagnetic while CrN4C6 has an antiferromagnetic ground state. The Curie temperatures are estimated by solving the anisotropic Heisenberg model with the Monte Carlo method.

Integration of Lysin into Chitosan Nanoparticles for Improving Bacterial Biofilm Inhibition.

Bacterial biofilms (BBFs) exhibit high drug resistance, antiphagocytosis, and extremely strong adhesion, and therefore can cause various diseases. They are also one of the important causes of bacterial infections. Thus, the effective removal of BBFs has attracted considerable research interest. Endolysins, which are efficient antibacterial bioactive macromolecules, have recently been receiving increasing attention. In this study, we overcame the deficiencies of endolysins via immobilization on chitosan nanoparticles (CS-NPs) by preparing LysST-3-CS-NPs using the ionic cross-linking reaction between CS-NPs and LysST-3, an endolysin purified using phage ST-3 expression. The obtained LysST-3-CS-NPs were verified and thoroughly characterized, their antimicrobial activity was investigated using microscopy, and their antibacterial efficacy on polystyrene surfaces was studied. The results obtained suggested that LysST-3-CS-NPs exhibit enhanced bactericidal properties and increased stability and can serve as reliable biocontrol agents for the prevention and treatment of Salmonella biofilm infections.

Effective triclosan removal by using porous aromatic frameworks in continuous fixed-bed column studies.

Triclosan (TCS) has been regarded as an emerging contaminant in aquatic systems, making its efficient removal of great significance. In this study, NPVMo@iPAF-1, with a specific surface area of 665 m2/g, was prepared by incorporating (NH4)5H6PV8Mo4O40 into porous aromatic frameworks (PAF). The maximum adsorption capacity of TCS on NPVMo@iPAF-1 reached 917.1 mg/g, as calculated from the Langmuir model. Fixed-bed columns packed with NPVMo@iPAF-1 were employed for TCS removal; the experiment data strongly correlated with the Thomas and Yoon-Nelson models under different operational conditions. Pore preservation, electrostatic effects, and the synergistic effect of π-π interactions contributed to the effective adsorption of TCS onto NPVMo@iPAF-1. The NPVMo@iPAF-1 fixed-bed column could be effectively regenerated through in-situ ozonation for more than 10 regeneration cycles. NPVMo@iPAF-1 turned out to be a promising adsorbent for removing TCS not only from pure water but also from reclaimed water and surface water samples.

An off-the-shelf small extracellular vesicle nanomedicine for tumor targeting therapy.

Small extracellular vesicles (sEVs) have shown excellent prospects as drug delivery systems for cancer therapy. However, the inherent non-targeting and short blood circulation characteristics severely restrict their practical applications as a delivery system. In addition, post-encapsulating drugs into sEVs also remains challenging. Here, we constructed an engineered cell line that secreted multifunctional sEVs (termed NBsEV204) with 7D12 (an anti-EGFR nanobody) and hCD47 decorations on their surface, as well as high levels of miR-204-5p encapsulation. NBsEV204 exhibited extended blood circulation and improved macrophage-mediated phagocytosis of tumor cells by blocking CD47 signaling. Importantly, NBsEV204 specifically targeted EGFR+ tumor cells and showed robust tumor-suppressive effects both in vitro and in vivo. Overall, this study provides a convenient and feasible method to produce off-the-shelf anticancer sEV nanomedicine, which exhibits tremendous potential for clinical translation.

Hemodynamic analysis of unilateral and bilateral renal artery stenosis based on fluid-structure interaction.

Renal artery stenosis (RAS) hypertension is a common type of secondary hypertension. This paper aimed to explore how unilateral renal artery stenosis (Uni-RAS) and bilateral renal artery stenosis (Bi-RAS) caused renovascular hypertension with the fluid-structure interaction (FSI) method. Based on a real RAS model, 20 ideal models with different stenosis degrees were established by modifying the stenosis segment. The hemodynamic parameters at different degrees of stenosis, mass flow rate (MFR), pressure drop (PD), fractional flow reserve (FFR), oscillatory shear index (OSI), and relative residence time (RRT), were numerically calculated by the computational fluid dynamics (CFD) method. The numerical results showed that RAS caused the decrease of MFR, and the increase of PD and the proportion of high OSI and high RRT. In the case of RAS, it could not be regarded as a reference indicator for causing renovascular hypertension that the value of FFR was greater than 0.9. In addition, the results of the statistical analysis indicated that Uni-RAS and Bi-RAS were statistically different for MFR, PD and the proportion of high RRT.

Oil spill detection on X-band marine radar images based on sea clutter fitting model.

Oil spills could cause great harm to the natural environment. The ability to identify them accurately is critical for prompt response and treatment. We proposed a sea clutter fitting model of marine radar images for oil spill detection. The model is derived from the geometric structure of the marine radar, the expression of marine radar received power, and the rough surface scattering model of the sea surface. In the denoised marine radar image, the sea clutter fitting model is used to detect coarse oil spills. Then the fine measurement is carried out by mean filter, the Otsu method, and noise reduction. The proposed oil spill detection method was used on radar images sampled after an oil spill accident happened in a coastal region in Dalian, China, on July 21, 2010. The proposed method can detect oil spills without human intervention, and the extracted oil spills are accurate and consistent with visual interpretation.

A Soft Capsule for Magnetically Driven Drug Delivery Based on a Hard-Magnetic Elastomer Foam.

Drug delivery systems based on porous soft biomaterials have been widely reported because of stimuli-responsive drug release and their inherent reservoirs for drug storage. Especially, magnetic-responsive porous soft biomaterials achieve rapid and real-time control of drug release due to the magnetic field-triggered large deformation. However, the drug release profiles of these materials are difficult to predict and repeat, which restrict them from releasing drugs in the required dosage. Here, we report a soft capsule based on a flexible hard-magnetic elastomer foam (HEF) for magnetically controlled on-demand drug delivery. The HEF capsule contains an inner HEF and an outer elastomer shell. The HEF exhibits low elastic modulus (10 kPa) and highly interconnected pores (81% interconnected pores). Benefitting from the novel precompressed magnetization, the compressive deformation of HEF reaches 66%. Thus, an adjustable drug release rate ranging from 0.02 to 1.7 mL/min in the HEF capsule is achieved. The deformation-triggered drug release profiles of the HEF capsule under the magnetic field are accurately predicted, allowing 85% accuracy in drug dosage regulation and more than 90% maximum cumulative drug release. Especially, the HEF capsule is proven capable of acting as a soft robot to perform magnetically driven drug delivery in a human stomach model. HEF can potentially serve as a soft robot for biomedical applications in the human body.

Pressure Driven Rapid Reconfigurable Liquid Metal Patterning.

This paper proposes a method for pressure driven rapid reconfigurable liquid metal patterning. A sandwich structure of "pattern-film-cavity" is designed to complete this function. Both sides of the highly elastic polymer film are bonded with two PDMS slabs. One PDMS slab has microchannels patterned on the surface. The other PDMS slab has a large cavity on its surface for liquid metal storage. These two PDMS slabs are bonded together, face to face, with the polymer film in the middle. In order to control the distribution of the liquid metal in the microfluidic chip, the elastic film will deform under the high pressure of the working medium in the microchannels and then extrude the liquid metal into different patterns in the cavity. This paper studies the factors of liquid metal patterning in detail, including external control conditions, such as the type and pressure of the working medium and the critical dimensions of the chip structure. Moreover, both a single-pattern and a double-pattern chip are fabricated in this paper, which can form or reconfigure the liquid metal pattern within 800 ms. Based on the above methods, reconfigurable antennas of two frequencies are designed and fabricated. Meanwhile, their performance is simulated and tested by simulation and vector network tests. The operating frequencies of the two antennas are respectively significantly switching between 4.66 GHz and 9.97 GHz.

Plexiform schwannomas of the sciatic nerve:a case report and review of the literature.

Background: Schwannomas grow slowly, mainly in the head and spine. The extremities schwannomas are rare and easily missed, particularly in patients who also have lumbar disc herniation in addition to sciatic schwannomas. We present a unique case of sciatic schwannoma , which has been considered as a lumbar disease in the past until an MRI of the thigh. Case presentation: A 43-year-old female complained of pain in her low back and left thigh for 10 years. Physical examination showed that her left thigh was swollen and positive Tinel sign. On MRI, we found a series of tumors suspected of schwannomas at the back of her left thigh. After obtaining the patient's consent, we performed intracapsular excision of her tumors. Histological examination of the tumors were consistent with plexiform schwannomas. The patient recovered well after operation and there was no sign of nerve injury or recurrence after follow-up for 11 months. We searched the Pubmed database and found 31 published reports about sciatic schwannomas. Conclusions: Sciatic schwannomas usually occur in middle-aged women, and the main symptom is pain. In addition to palpation, we should pay attention to Tinel sign during physical examination. MRI is very helpful for diagnosis, but histological examination is the only way to make a final diagnosis. Intracapsular resection is the best method for the treatment of schwannomas, although there is still the possibility of recurrence after operation.

Adsorption Behavior and Mechanism of Cesium Ions in Low-Concentration Brine Using Ammonium Molybdophosphate-Zirconium Phosphate on Polyurethane Sponge.

Salt lake brine originating from Qinghai, China has abundant cesium resources and huge total reserves. The inorganic ion exchangers ammonium molybdophosphate (AMP) and zirconium phosphate (ZrP) have the significant advantages of separating and extracting Cs+ as a special adsorbent. Nevertheless, their high solubility in water leads to a decrease in their ability to adsorb Cs+ in aqueous solutions, causing problems such as difficulty with using adsorbents alone and a difficult recovery. In this work, an environmentally friendly polyurethane sponge (PU sponge) with a large specific surface area is employed as an adsorbent carrier by physically impregnating dopamine-coated AMP and ZrP onto a PU sponge, respectively. The experiment found that under the same conditions, the AMP/PU sponge performs better than the ZrP/PU sponge for Cs+ adsorption. When the amount of adsorbent reaches 0.025 g, the adsorption capacity reaches saturation. The adsorption efficiency remains above 80% when the concentration of Cs+ is 5-35 mg/L. The kinetic calculations show that adsorption is spontaneous, feasible, and has a higher driving force at high temperatures. In addition, the power and mechanism of the interaction between adsorbent and adsorbent are explained using the density functional theory calculation. This efficient, stable, and selective Cs+ adsorbent provides design guidelines.

Bacteriophage Endolysin: A Powerful Weapon to Control Bacterial Biofilms.

Bacterial biofilms are widespread in the environment, and bacteria in the biofilm are highly resistant to antibiotics and possess host immune defense mechanisms, which can lead to serious clinical and environmental health problems. The increasing problem of bacterial resistance caused by the irrational use of traditional antimicrobial drugs has prompted the search for better and novel antimicrobial substances. In this paper, we review the effects of phage endolysins, modified phage endolysins, and their combination with other substances on bacterial biofilms and provide an outlook on their practical applications. Phage endolysins can specifically and efficiently hydrolyze the cell walls of bacteria, causing bacterial lysis and death. Phage endolysins have shown superior bactericidal effects in vitro and in vivo, and no direct toxicity in humans has been reported to date. The properties of phage endolysins make them promising for the prevention and treatment of bacterial infections. Meanwhile, endolysins have been genetically engineered to exert a stronger scavenging effect on biological membranes when used in combination with antibiotics and drugs. Phage endolysins are powerful weapons for controlling bacterial biofilms.

Infiltration of a Unique CD8+CD274+ Cell Subgroup in Hepatocellular Carcinoma is Associated with Poor Clinical Outcomes.

Introduction: Immune checkpoint (IC) inhibitor-related immunotherapies have attracted considerable attention in hepatocellular carcinoma (HCC). High IC expression and high tumor infiltrating lymphocyte levels are the current indicators of sensitivity to IC inhibitors. Thus, it is imperative to apply precision medicine strategies for patient selection. Methods: Six independent HCC cohorts were used for analysis at the single-cell and tissue levels. Multiplex immunofluorescence and immunochemistry staining assays were used to validate our results. A series of methodologies were used for immune-related evaluations. Results: Herein, we uncovered a unique CD8+CD274+ cell subpopulation that is associated with tumor progression and poor survival in HCC at the single-cell level. We assessed this subset at the tissue level and found that the prognostic significance of CD274 is dependent on CD8A expression in HCC. Subsequently, we identified a unique high-risk subpopulation that showed high CD8A expression coupled with intense CD274 expression in multiple HCC cohorts. CD8AHighCD274High* subgroup was correlated with malignant indexes and remained an independent prognostic factor when considering the influence of these indexes. Molecular characteristic analyses showed that the CD8AHighCD274High* subgroup harbored more mutations, had higher immune response activity and presented enrichment of cancer-related biological processes. Moreover, this high-risk subpopulation in HCC was characterized by high immune cell infiltration, low tumor purity, and enrichment of cancer-related signatures. Finally, cases with this phenotype demonstrated higher immunomodulator and IC levels and greater sensitivity to IC inhibitors. Conclusion: Our findings illustrate that some HCC patients may have a poor prognosis despite high CD8+ T-cell infiltration. These patients would probably benefit from IC inhibitor-based combination treatment.

Activating and optimizing the In-Plane interface of 1 T/2H MoS2 for efficient hydrogen evolution reaction.

Implanting the octahedral phase (1 T) into the hexagonal phase (2H) of the molybdenum disulfide (MoS2) matrix is considered one of the effective methods to enhance hydrogen evolution reaction (HER) performances of MoS2. In this paper, hybrid 1 T/2H MoS2 nanosheets array was successfully grown on conductive carbon cloth (1 T/2H MoS2/CC) via facile hydrothermal method and the 1 T phase content in 1 T/2H MoS2 is regulated to gradually increase from 0 % to 80 %. 1 T/2H MoS2/CC with 75 % 1 T phase content exhibits optimal HER performances. The DFT calculation results show that S atoms in 1 T/2H MoS2 interface exhibit the lowest hydrogen adsorption Gibbs free energies (ΔGH*) compared with other sites. The improvement of HER performances are primarily attributed to activating the in-plane interface regions of the hybrid 1 T/2H MoS2 nanosheets. Furthermore, the relationship between 1 T MoS2 content in 1 T/2H MoS2 and catalytic activity was simulated by a mathematical model, which shows that the catalytic activity presents a trend of increasing and then decreasing with the increase of 1 T phase content.

Liquid Metal-Based Electrode Array for Neural Signal Recording.

Neural electrodes are core devices for research in neuroscience, neurological diseases, and neural-machine interfacing. They build a bridge between the cerebral nervous system and electronic devices. Most of the neural electrodes in use are based on rigid materials that differ significantly from biological neural tissue in flexibility and tensile properties. In this study, a liquid-metal (LM) -based 20-channel neural electrode array with a platinum metal (Pt) encapsulation material was developed by microfabrication technology. The in vitro experiments demonstrated that the electrode has stable electrical properties and excellent mechanical properties such as flexibility and bending, which allows the electrode to form conformal contact with the skull. The in vivo experiments also recorded electroencephalographic signals using the LM-based electrode from a rat under low-flow or deep anesthesia, including the auditory-evoked potentials triggered by sound stimulation. The auditory-activated cortical area was analyzed using source localization technique. These results indicate that this 20-channel LM-based neural electrode array satisfies the demands of brain signal acquisition and provides high-quality-electroencephalogram (EEG) signals that support source localization analysis.

Direct Nitration of Vinylcycles with Copper Nitrate.

A direct nitration of vinylcyclopropanes is disclosed with Cu(NO3)2 and KI in a regio- and stereoselective manner to afford nitroalkenes efficiently, where the cyclopropane skeleton was retained. The given method could be extended to other vinylcycles as well as biomolecule derivatives with wide substrate scope, good functionality tolerance, and efficient synthesis modularity. Further transformations illustrated the obtained products as versatile building blocks in organic synthesis. The proposed ionic pathway could account for the untouched small ring and the effect of KI during the reaction.

Microstructure and Mechanical Properties of Nanoparticulate Y2O3 Modified AlSi10Mg Alloys Manufactured by Selective Laser Melting.

AlSi10Mg has a good forming ability and has been widely accepted as an optimal material for selective laser melting (SLM). However, the strength and elongation of unmodified AlSi10Mg are insufficient, which limits its application in the space industry. In this paper, yttrium oxide (Y2O3) nanoparticles modified AlSi10Mg composites that were manufactured using SLM. The effects of Y2O3 nanoparticles (0~2 wt.% addition) on the microstructure and mechanical properties of AlSi10Mg alloys were investigated. An ultimate tensile strength of 500.3 MPa, a yield strength of 322.3 MPa, an elongation of 9.7%, a good friction coefficient of 0.43, and a wear rate of (3.40 ± 0.09) ×10-4 mm3·N-1·m-1 were obtained with the addition of 0.5 wt.% Y2O3 nanoparticles, and all these parameters were higher than those of the SLMed AlSi10Mg alloy. The microhardness of the composite with 1.0 wt.% Y2O3 reached 145.6 HV0.1, which is an increase of approximately 22% compared to the unreinforced AlSi10Mg. The improvement of tensile properties can mainly be attributed to Orowan strengthening, fine grain strengthening, and load-bearing strengthening. The results show that adding an appropriate amount of Y2O3 nanoparticles can significantly improve the properties of the SLMed AlSi10Mg alloy.